Pyrotinib Rechallenge in Her2-positive Metastatic Breast Cancer Pretreated With Pyrotinib and Trastuzumab

Inclusion Criteria: 1. Aged ≥18 and ≤75 years; 2. Pathologically confirmed HER2 positive patients with recurrence/ metastatic breast cancer: HER2 IHC 3+, or HER2 IHC 2+ and FISH detection gene amplification; 3. History of trastuzumab-containing chemotherapy in neoadjuvant, adjuvant or recurrence/ metastatic setting; 4. History of pyrotinib-containing chemotherapy in neoadjuvant or recurrence/ metastatic setting; 5. Previously reveived ≤2 systemic treatment in recurrence/ metastasis setting; (anti-HER2 ADCs such as T-DM1 is included in chemotherapy regimens, endocrine therapy alone is not included); 6. ECOG performance status of 0 to 1; 7. According to RECIST 1.1, at least one extracranial measurable lesion exists； 8. Signed informed consent. Exclusion Criteria: 1. Patients with leptomeningeal metastasis or unstable brain metastasis; 2. History of neurological or psychiatric disorders; 3. Second malignancies within 5 years, except for cured skin basal cell carcinoma, carcinoma in-situ of uterine cervix and squamous-cell carcinoma; 4. Undergone major surgical procedures or significant trauma within 4 weeks prior to randomization, or expected to undergo major surgery. 5. Factors influencing the usage of oral administration (e.g. unable to swallow, chronic diarrhea and intestinal obstruction, etc.); 6. History of allergies to the drug components of this regimen; 7. History of Immunodeficiency, acquired or congenital immunodeficiency (HIV positive), history of organ transplantation; 8. Any other situations judged by investigator as not suitable for participating in this study.